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Β-GPA administration activates slow oxidative muscle signaling pathways and protects soleus muscle against the increased fatigue under 7-days of rat hindlimb suspension.
Archives of Biochemistry and Biophysics 2023 May 24
Unloading of slow-twitch muscles results in increased muscle fatigue and the mechanisms of this effect are poorly studied. We aimed to analyze the role of high-energy phosphates accumulation during the first week of rat hindlimb suspension plays in a fiber-type phenotype shift towards fast-type fatigable muscle fibers. Male Wistar rats were divided into 3 groups (n = 8): C - vivarium control; 7HS - 7-day hindlimb suspension; 7HB - 7-day hindlimb suspension with intraperitoneal injection of beta-guanidine propionic acid (β-GPA, 400 mg/kg b w). β-GPA is a competitive inhibitor of creatine kinase and it reduces concentrations of ATP and phosphocreatine. In the 7HB group, β-GPA treatment protected a slow-type signaling network in an unloaded soleus muscle, including MOTS-C, AMPK, PGC1 α and micro-RNA-499. These signaling effects resulted in a preserved soleus muscle fatigue resistance, slow-type muscle fibers percentage and mitochondrial DNA copy number under muscle unloading.
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